Project Summary/Abstract The discovery of iPSCs provides an unprecedented opportunity for any scientist to derive an inexhaustible supply of patient-derived primary cells. These cells containing each patient's own genetic background can now be applied for in vitro human disease modeling, drug screening of personalized therapeutics, and the development of future regenerative cell-based therapies. The most valuable human clones already generated by the CTSA investigators collaborating on this proposal not only carry common disease-associated mutations and polymorphisms, but also carry knock-in fluorochrome reporters targeted to specific loci through state-of-the-art gene editing technologies. The goal of this proposal is the establishment of a CTSA network of induced pluripotent stem cell (iPSC) repositories and iPSC cores that will enable advanced disease modeling using >1000 existing normal and disease specific human cell lines and banking 6,000 additional samples procured from the 2nd and 3rd generation participants of the Framingham Study. A concerted effort for curation, sharing, and distribution of this vital resource across all CTSAs does not exist. This proposal thus creates a CTSA iPSC Network led by teams who have championed an `Open Source Biology' approach, freely sharing iPSC lines and their reprogramming reagents with more than 500 labs to date across the globe. Its goals are to make patient-derived iPSCs together with the tools and expertise for their genetic manipulation available to the greater research community on a large scale to realize their promise for extending understanding of disease and developing potential therapies. To achieve these goals, it proposes: a) national sharing of >1000 iPSC lines already derived by the CTSA teams collaborating in this proposal, representing a critical resource in high demand by both basic and clinical researchers, b) development and support of formalized education and training programs able to nationally disseminate the expertise required to fully harness these new tools and differentiate them into the wide diversity of human cell lineages, c) maintenance and sharing of open source gene-editing tools and gene edited iPSC lines that will enable CTSA investigators to manipulate the human genome at will, and d) derivation for national sharing of additional iPSC lines generated from the most densely clinically and genetically phenotyped cohort of individuals currently followed in the USA today: the ~6,000 participants of the second and third generations of the Framingham Study.